tbuckley/cabot-search huggingface dataset:
Statin Use for the Primary Prevention of Cardiovascular Disease in Adults
Authors: Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael Cabana, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, John M. Ruiz, James Stevermer, John B. Wong
Journal: JAMA (2022)

<h3>Importance</h3> Cardiovascular disease (CVD) is the leading cause of morbidity and death in the US and is the cause of more than 1 of every 4 deaths. Coronary heart disease is the single leading cause of death and accounts for 43% of deaths attributable to CVD in the US. In 2019, an estimated 558 000 deaths were caused by coronary heart disease and 109 000 deaths were caused by ischemic stroke. <h3>Objective</h3> To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality or all-cause mortality. <h3>Population</h3> Adults 40 years or older without a history of known CVD and who do not have signs and symptoms of CVD. <h3>Evidence Assessment</h3> The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD event risk of 10% or greater has at least a moderate net benefit. The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more of these CVD risk factors and an estimated 10-year CVD event risk of 7.5% to less than 10% has at least a small net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of statin use for the primary prevention of CVD events and mortality in adults 76 years or older with no history of CVD. <h3>Recommendation</h3> The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk of 10% or greater. (B recommendation) The USPSTF recommends that clinicians selectively offer a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more of these CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%. The likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating a statin for the primary prevention of CVD events and mortality in adults 76 years or older. (I statement)
Quantifiable brain atrophy synthesis for benchmarking of cortical thickness estimation methods
Authors: Filip Rusak, Rodrigo Santa Cruz, Léo Lebrat, Ondrej Hlinka, Jurgen Fripp, Elliot Smith, Clinton Fookes, Andrew P. Bradley, Pierrick Bourgeat
Journal: Medical Image Analysis (2022)

Cortical thickness (CTh) is routinely used to quantify grey matter atrophy as it is a significant biomarker in studying neurodegenerative and neurological conditions. Clinical studies commonly employ one of several available CTh estimation software tools to estimate CTh from brain MRI scans. In recent years, machine learning-based methods emerged as a faster alternative to the main-stream CTh estimation methods (e.g. FreeSurfer). Evaluation and comparison of CTh estimation methods often include various metrics and downstream tasks, but none fully covers the sensitivity to sub-voxel atrophy characteristic of neurodegeneration. In addition, current evaluation methods do not provide a framework for the intra-method region-wise evaluation of CTh estimation methods. Therefore, we propose a method for brain MRI synthesis capable of generating a range of sub-voxel atrophy levels (global and local) with quantifiable changes from the baseline scan. We further create a synthetic test set and evaluate four different CTh estimation methods: FreeSurfer (cross-sectional), FreeSurfer (longitudinal), DL+DiReCT and HerstonNet. DL+DiReCT showed superior sensitivity to sub-voxel atrophy over other methods in our testing framework. The obtained results indicate that our synthetic test set is suitable for benchmarking CTh estimation methods on both global and local scales as well as regional inter-and intra-method performance comparison.
Taking cognizance of the risks associated with COVID-19, vaccine, and treatment in liver transplant recipients – A commentary on “The urgency of the Covid-19 vaccine in liver transplantation patients: What, how, and when?” [Int. J. Surg. 100 (Suppl) (2022) 106492)]
Authors: ArunSundar MohanaSundaram, Shanmugarajan Thukani Sathanantham, Ravichandiran Velayutham
Journal: International Journal of Surgery (2022)
Virus variant–specific clinical performance of SARS coronavirus two rapid antigen tests in point-of-care use, from November 2020 to January 2022
Authors: Isabell Wagenhäuser, Kerstin Knies, Daniela Hofmann, Vera Rauschenberger, Michael Eisenmann, Julia Reusch, Alexander Gabel, Sven Flemming, Oliver Andres, Nils Petri, Max S. Topp, Michael Papsdorf, Miriam McDonogh, Raoul Verma-Führing, Agmal Scherzad, Daniel Zeller, Hartmut Böhm, Anja Gesierich, Anna K. Seitz, Michael Kiderlen, Micha Gawlik, Regina Taurines, Thomas Wurmb, Ralf-Ingo Ernestus, Johannes Forster, Dirk Weismann, Benedikt Weißbrich, Lars Dölken, Johannes Liese, Lars Kaderali, Oliver Kurzai, Ulrich Vogel, Manuel Krone
Journal: Clinical Microbiology and Infection (2022)
Clinical azole cross-resistance in Candida parapsilosis is related to a novel MRR1 gain-of-function mutation
Authors: Joana Branco, Adam P. Ryan, Ana Pinto e Silva, Geraldine Butler, Isabel M. Miranda, Acácio G. Rodrigues
Journal: Clinical Microbiology and Infection (2022)

Hereby, we describe the molecular mechanisms underlying the acquisition of azole resistance by a Candida parapsilosis isolate following fluconazole treatment due to candiduria.A set of three consecutive C. parapsilosis isolates were recovered from the urine samples of a patient with candiduria. Whole-genome sequencing and antifungal susceptibility assays were performed. The expression of MRR1, MDR1, ERG11 and CDR1B (CPAR2_304370) was quantified by RT-qPCR.The initial isolate CPS-A was susceptible to all three azoles tested (fluconazole, voriconazole and posaconazole); isolate CPS-B, collected after the second cycle of treatment, exhibited a susceptible-dose-dependent phenotype to fluconazole and isolate CPS-C, recovered after the third cycle, exhibited a cross-resistance profile to fluconazole and voriconazole. Whole-genome sequencing revealed a putative resistance mechanism in isolate CPS-C, associated with a G1810A nucleotide substitution, leading to a G604R change in the Mrr1p transcription factor. Introducing this mutation into the susceptible CPS-A isolate (MRR1RI) resulted in resistance to fluconazole and voriconazole, as well as up-regulation of MRR1 and MDR1. Interestingly, the susceptible-dose-dependent phenotype exhibited by isolate CPS-B was associated with an increased copy number of the CDR1B gene. The expression of CDR1B was increased in both isolates CPS-B and CPS-C and in the MRR1RI strain, harbouring the gain-of-function mutation.Our results describe clinical azole cross-resistance acquisition in C. parapsilosis due to a G1810A (G604R) gain-of-function mutation, resulting in MRR1 hyperactivation and consequently, MDR1 efflux pump overexpression. We also associated amplification of the CDR1B gene with decreased fluconazole susceptibility and showed that it is a putative target of the MRR1 gain-of-function mutation.
Clinical characteristics and 1‐year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association <scp>Database‐Heart</scp> Failure Center Registry
Authors: Anping Cai, Weida Qiu, Yingling Zhou, Yingqing Feng, Jiyan Chen, Shuang Xia, Weimin Li, Yuhua Liao, Xinli Li, Jingmin Zhou, Hua Wang, Wei Jin, Qing Zhang, Zhijun Sun, Mulei Chen, Jiang Wang, Hong Kong, Yao Zhang, Wei Dong, Ling Bai, Dongjie Xu, Jing Yuan, Chen Liu, Meng Jiang, Yamei Xu, Liwen Li, Yugang Dong, Jiefu Yang
Journal: European Journal of Heart Failure (2022)
Albiglutide in patients with type 2 diabetes and heart failure: a post‐hoc analysis from Harmony Outcomes
Authors: João Pedro Ferreira, Abhinav Sharma, Francisco Vasques-Nóvoa, António Angélico-Gonçalves, Ana Rita Leite, Marta Borges-Canha, Davide Carvalho, Milton Packer, Faiez Zannad, Adelino Leite-Moreira, João Sérgio Neves
Journal: European Journal of Heart Failure (2022)
Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy
Authors: Alba Maestro‐Benedicto, Paula Vela, Fernando de Frutos, Nerea Mora, Antonia Pomares, Emiliano Gonzalez‐Vioque, Ana Briceño, Eva Cabrera, Marta Cobo‐Marcos, Fernando Dominguez, Esther Gonzalez‐Lopez, Javier Segovia, Enrique Lara‐Pezzi, Pablo Garcia‐Pavia
Journal: European Journal of Heart Failure (2022)

Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild‐type transthyretin amyloidosis is the most frequent form of ATTR‐CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR‐CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population. Methods and results Prevalence of ATTRv in elderly ATTR‐CM patients (≥70 years) was assessed in a cohort of 300 consecutive ATTR‐CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% female, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95% confidence interval [CI] 3.1–8.8) and 13 (5.3%; 95% CI 5.6–26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR‐CM was 13% (95% CI 2.1–23.5). Univariate analysis identified female sex (odds ratio [OR] 3.66; 95% CI 1.13–11.85; p = 0.03), black ancestry (OR 46.31; 95% CI 3.52–Inf; p = 0.005), eye symptoms (OR 6.64; 95% CI 1.20–36.73; p = 0.03) and polyneuropathy (OR 10.05; 95% CI 3.09–32.64; p &lt; 0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR‐CM patients allowed initiation of transthyretin‐specific drug treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers. Conclusions Hereditary transthyretin amyloidosis is present in a substantial number of ATTR‐CM patients aged ≥70 years. Identification of ATTRv in elderly patients with ATTR‐CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR‐CM regardless of age.
Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study
Authors: Uwe Platzbecker, Katharina S. Götze, Philipp Kiewe, Ulrich Germing, Karin Mayer, Markus Radsak, Thomas Wolff, Joerg Chromik, Katja Sockel, Uta Oelschlägel, Detlef Haase, Thomas Illmer, Haifa Kathrin Al-Ali, Gerda Silling, Joseph G. Reynolds, Xiaosha Zhang, Kenneth M. Attie, Jeevan K. Shetty, Aristoteles Giagounidis
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Luspatercept has high clinical activity in patients with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS) and ring sideroblasts (RS) relapsed or refractory to erythropoietin. We report long-term luspatercept safety and efficacy in 108 patients with LR-MDS in the PACE-MDS study, including 44 non-RS and 34 non-transfusion-dependent or previously untreated patients. The primary end point was safety. Secondary end points included rates of hematologic improvement (HI) erythroid (HI-E), HI neutrophil, and HI platelet. Exploratory end points included erythropoiesis biomarker quantitation and mutation data. Median duration of luspatercept exposure was 315 days (range, 21-1,934 days). No new safety signals emerged. HI-E was observed in 53.7% of patients, including 36.4% of non-RS and 70.6% of non-transfusion-dependent patients. HI neutrophil and HI platelet were observed in 33.3% and 9.5% of patients, respectively. An almost three-fold increase in bone marrow late to early progenitor cell ratio accompanied HI-E response, irrespective of RS status. Lower baseline erythropoietin levels in non-RS patients (69.6 v 623.3 IU/L; P = .0077) and higher late to early erythroid progenitor cell ratio (10.44 v 4.48; P = .0106) in RS patients were associated with HI-E. This study highlights luspatercept's effects across LR-MDS subtypes, including untreated MDS-RS, serving as a platform for future trials.
Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma
Authors: Jason A. Chesney, Antoni Ribas, Georgina V. Long, John M. Kirkwood, Reinhard Dummer, Igor Puzanov, Christoph Hoeller, Thomas F. Gajewski, Ralf Gutzmer, Piotr Rutkowski, Lev Demidov, Petr Arenberger, Sang Joon Shin, Pier Francesco Ferrucci, Andrew Haydon, John Hyngstrom, Johannes V. van Thienen, Sebastian Haferkamp, Josep Malvehy Guilera, Bernardo Leon Rapoport, Ari VanderWalde, Scott J. Diede, James R. Anderson, Sheryl Treichel, Edward L. Chan, Sumita Bhatta, Jennifer Gansert, Frank Stephen Hodi, Helen Gogas
Journal: Journal of Clinical Oncology (2022)

The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma.Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis.Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm.T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.
Right ventricular dysfunction predicts outcome after transcatheter mitral valve repair for primary mitral valve regurgitation
Authors: Philipp M. Doldi, Lukas Stolz, Daniel Kalbacher, Benedikt Köll, Martin Geyer, Sebastian Ludwig, Mathias Orban, Daniel Braun, Ludwig T. Weckbach, Thomas J. Stocker, Michael Näbauer, Satoshi Higuchi, Tobias Ruf, Jaqueline Da Rocha e Silva, Mirjam Wild, Noemie Tence, Matthias Unterhuber, Niklas Schofer, Aniela Petrescu, Holger Thiele, Philipp Lurz, Edith Lubos, Stephan von Bardeleben, Nicole Karam, Daryoush Samim, Jean‐Michel Paradis, Christos Iliadis, Erion Xhepa, Christian Hagl, Steffen Massberg, Jörg Hausleiter
Journal: European Journal of Heart Failure (2022)

Right ventricular dysfunction (RVD), as expressed by right ventricular to pulmonary artery coupling, has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (MR). The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality.This multicentre study included patients undergoing M-TEER for symptomatic PMR at nine international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. A total of 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.47-3.81, p < 0.001), which was confirmed in the VC (HR 2.06, 95% CI 1.36-3.13, p < 0.001). Procedural success (MR ≤2+) and symptomatic improvement at follow-up (New York Heart Association [NYHA] class ≤II) were lower in PMR patients with RVD (MR ≤2+: 82% vs. 93%, p = 0.002; NYHA class ≤II: 57.3% vs. 66.5%, p = 0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR 2.23, 95% CI 1.63-3.05, p < 0.001).Mitral valve edge-to-edge repair is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into pre-procedural prognostic considerations.
Effects of remote haemodynamic‐guided heart failure management in patients with different subtypes of pulmonary hypertension: insights from the <scp>MEMS‐HF</scp> study
Authors: Birgit Assmus, Christiane E. Angermann, Basil Alkhlout, Folkert W. Asselbergs, Steffen Schnupp, Jasper J. Brugts, Peter Nordbeck, Qian Zhou, Marie‐Elena Brett, Greg Ginn, Philip B. Adamson, Michael Böhm, Stephan Rosenkranz
Journal: European Journal of Heart Failure (2022)

The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary artery pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) class III outpatients with at least one heart failure hospitalization (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH).In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p = 0.029) and pulmonary artery compliance lower (p = 0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PAPs declined in IpcPH and CpcPH subgroups (all p < 0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p < 0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/patient-year; hazard ratio [HR] 0.37) and IpcPH (0.72 events/patient-year; HR 0.45) patients. Participants without PH benefited most (0.26 events/patient-year; HR 0.17, p = 0.04 vs. IpcPH/CpcPH patients). Quality of life and NYHA class improved significantly in all subgroups.Outpatients with NYHA class III symptoms with at least one HFH during 1 year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline.
Device‐based remote monitoring strategies for congestion‐guided management of patients with heart failure: a systematic review and meta‐analysis
Authors: Andrea Zito, Giuseppe Princi, Giulio Francesco Romiti, Mattia Galli, Stefania Basili, Giovanna Liuzzo, Tommaso Sanna, Attilio Restivo, Giuseppe Ciliberti, Carlo Trani, Francesco Burzotta, Alfredo Cesario, Gianluigi Savarese, Filippo Crea, Domenico D'Amario
Journal: European Journal of Heart Failure (2022)

Pre-clinical congestion markers of worsening heart failure (HF) can be monitored by devices and may support the management of patients with HF. We aimed to assess whether congestion-guided HF management according to device-based remote monitoring strategies is more effective than standard therapy.A comprehensive literature research for randomized controlled trials (RCTs) comparing device-based remote monitoring strategies for congestion-guided HF management versus standard therapy was performed on PubMed, Embase, and CENTRAL databases. Incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) were calculated using the Poisson regression model with random study effects. The primary outcome was a composite of all-cause death and HF hospitalizations. Secondary endpoints included the individual components of the primary outcome. A total of 4347 patients from eight RCTs were included. Findings varied according to the type of parameters monitored. Compared with standard therapy, haemodynamic-guided strategy (4 trials, 2224 patients, 12-month follow-up) reduced the risk of the primary composite outcome (IRR 0.79, 95% CI 0.70-0.89) and HF hospitalizations (IRR 0.76, 95% CI 0.67-0.86), without a significant impact on all-cause death (IRR 0.93, 95% CI 0.72-1.21). In contrast, impedance-guided strategy (4 trials, 2123 patients, 19-month follow-up) did not provide significant benefits.Haemodynamic-guided HF management is associated with better clinical outcomes as compared to standard clinical care.